November 18th, 2019

PAScal Enabled Off-the-Shelf and Personalized Antigen-Based Cancer Vaccine Development

Treos Bio Personal Antigen Selection Calculator platform addresses both patient and tumor heterogeneity

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A London-based company announced the development of a unique approach creating cancer vaccines by focusing not just on the vaccine targets, but also on delivering antigen targets to which each patient’s immune system can specifically respond. 

On November 7, 2019, Treos Bio said in a press release its ‘Personal Antigen Selection Calculator (PASCal) platform addresses both patient and tumor heterogeneity.’

PASCal has a unique, validated algorithm for the selection of Personal EPItopes (PEPIs) that are likely to induce antigen-specific T cell responses in a subject based on the patients’ complete HLA-genotype. 

PAScal enabled the development of 2 families of effective shared antigen-based cancer vaccines (“off-the-shelf” and “personalized”) that target 19 cancer indications.

Furthermore, these families are commercially scalable, without the need for tumor biopsy and on-demand manufacturing.

  • P329 PolyPEPI1018 off-the-shelf vaccine as an add-on to maintenance therapy achieved durable treatment responses in patients with microsatellite-stable metastatic colorectal cancer patients (MSS mCRC);
  • P677 Warehouse approach for the development of personalized cancer vaccines by using Personal Antigen Selection Calculator (PASCal) without the need for tumor biopsy.

Treos Bio uses a knowledgebase and algorithm embedded in its proprietary PASCal tool to develop cancer vaccines. 

This knowledgebase contains a comprehensive taxonomy of immunological information linking the HLA genetics of 26,000 subjects to tumor-specific antigens derived from over 96,000 tumor biopsies, resulting in 10^8 true HLA-epitope pairs (both HLA class I and class II molecules). 

The PolyPEPI1018 “off-the-shelf” cancer vaccine achieved unprecedented immune and tumor responses in MSS mCRC patients as an add-on to maintenance therapy in a Phase 1/2 clinical trial (OBERTO), interim results of which were presented at ASCO 2019 and ESMO 2019. 

The results to be presented at SITC 2019 demonstrated improvements in progression-free survival (PFS) that compare favorably to those observed with the first-line maintenance therapy alone, based on historical benchmark data.

“At 9 months median follow-up, the median PFS was not reached with three of six patients controlling their disease for at least ten months, thereby delaying the need for 2nd line treatment,” said Joleen M. Hubbard M.D., principal investigator of the OBERTO trial at the Mayo Clinic.

The improvements in clinical benefit were consistent with the immunological responses observed at both peripheral and tumor level. 

Specifically, HalioDx proprietary assay Immunoscore® CR TL (CD3/CD8) revealed that vaccination-induced recruitment of tumor-infiltrating lymphocytes (TILs) to both the invasive margin and core tumor area for three out of four patients’ biopsies tested. 

For two patients experiencing tumor regression and prolonged control of the disease, CD3+ and CD8+ cytotoxic T cells accumulated in the core tumor post-vaccination, turning them into inflamed, immunologically “hot” tumors.

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“These clinical results, together with the unprecedented autologous HLA-dependent vaccine antigen-specific immune responses observed at both peripheral and tumor level, provide the sequence of evidence for the vaccine’s mode of action against the tumor, in vivo,” said Dr. Eniko R. Toke, Chief Scientific Officer of Treos Bio.

For the development and production of off-the-shelf personalized vaccines, Treos Bio has designed the PEPI Panel, a library of vaccine peptides that contains almost 3,300 immunogenic peptides derived from 184 frequently expressed, shared tumor antigens associated with and shared between 19 cancer indications. 

PASCal selects the patient-specific immunogenic vaccine peptides based on the patients’ complete HLA-set, frequently expressed antigens specific to the patient’s tumor with no tumor biopsy required from the patient, only a saliva sample. 

Personalized vaccines administered to 3 HLA-genotyped metastatic cancer patients (with ovarian-, breast- and colorectal cancer) induced CD8+ T-cell responses against an average of 12 different vaccine antigens, from the 12-13 vaccine peptides administered for each patient. 

Long-lasting CD8+ T-cell responses were also detected 14 months after the last vaccination. The vaccinations boosted the pre-existing T-cell reactivities against multiple antigens, demonstrating their presence in the patients’ tumor and confirming the success of the vaccine design strategy, which aims to induce polyclonal T-cell responses against at least three antigens expressed by the tumor.

“These results are very promising. Treos is the first in the immunotherapy field to generate positive data for classically cold tumors: MSS mCRC, ovarian cancer, and breast cancer,” said Christopher C. Gallen, M.D., Ph.D., and Chairman of Treos Bio, in the related press release.

“Our vaccines have the potential to overcome the limitations of other vaccines and unlike other approaches to personalized cancer vaccination, there is no need for tumor biopsy. Moreover, the proposed treatment process is highly efficient and commercially scalable,” concluded Dr. Gallen.

The full abstracts are available: Warehouse approach for the development of personalized cancer vaccines by using Personal Antigen Selection Calculator (PASCal) without need for tumor biopsy and PolyPEPI1018 off-the shelf vaccine as add-on to maintenance therapy achieved durable treatment responses in patients with microsatellite-stable metastatic colorectal cancer patients (MSS mCRC).

The presentations will be available at Treos Bio on November 11, 2019, at 13.00 CET.

Treos Bio uses data science and proprietary biomarkers to develop its precision cancer vaccines, with substantially shortened development timelines and at lower costs. Treos Bio’s off-the-shelf cancer vaccines are designed to exclude autoimmunity and induce tumor-specific immune responses to be safer and more effective in patients who cannot benefit from current immunotherapies. 

Cancer Vaccine news published by Precision Vaccinations